Micronutrient deficiencies, especially those arising from zinc (Zn) and iron (Fe), pose serious human health problems for more than 2 billion people worldwide. Wheat is a major source of dietary energy and protein for the world’s growing population, and its potential to assist in reducing micronutrient-related malnutrition can be enhanced via integration of agronomic fertilization practices and delivery of genetically-manipulated, micronutrient rich wheat varieties. Targeted breeding for these biofortified varieties was initiated by exploiting available genetic diversity for Zn and Fe from wild relatives of cultivated wheat and synthetic hexaploid progenitors. The proof-of-concept results from the performance of competitive biofortified wheat lines showed good adaptation in target environments without compromising essential core agronomic traits. Agronomic biofortification through fertilizer approaches could complement the existing breeding approach; for instance, foliar application of Zn fertilizer can increase grain Zn above the breeding target set by nutritionists. This review synthesizes the progress made in genetic and agronomic biofortification strategies for Zn and Fe enrichment of wheat.